Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints

1. A method of treating an inflamed orthopedic joint in a human or an animal, said joint comprising: i) opposing hyaline cartilage articular surfaces; ii) peripheral to the surfaces, a central joint space comprising a collagenous capsule; and iii) synovial fluid contained within the joint space, the method comprising directly administering into the joint space by trans-capsular administration a formulation comprising an effective amount of a compound of one of the following structural formulas:

or a salt thereof.

2. The method of claim 1 , wherein the administration is through a needle.

3. The method of claim 1 , wherein the administration is through a drug pump.

4. The method of claim 1 , wherein the administration is by injection into the synovial fluid.

5. The method of claim 1 , wherein a portion of the synovial fluid is removed prior to administering the formulation.

6. The method of claim 1 , wherein the formulation further comprises at least one additional therapeutic agent.

7. The method of claim 6 , wherein the additional therapeutic agent is selected from the group consisting of:

i) a growth factor,

ii) mesenchymal stem cells, adult stem cells and embryonic stem cells,

iii) an MMP antagonist,

iv) a monoclonal anti-TNFα antibody,

v) rapamycin,

vi) a COX-2 antagonist,

vii) an antagonist of nitric oxide synthase,

viii) an anti-oxidant,

ix) an anti-proliferative agent,

x) an anti-apoptotic agent,

xi) a non-steroidal anti-inflammatory agent,

xii) glycosaminoglycans,

xiii) microparticles,

xiv) a caspase inhibitor,

xv) an inhibitor of pro-inflammatory interleukin,

xvi) an inhibitor of PLA 2 viscosupplement,

xvii) tetracycline analogs, and

xviii) IGFI and II.

8. The method of claim 6 , wherein the additional therapeutic agent is a non-steroidal anti-inflammatory agent.

9. The method of claim 8 , wherein the non-steroidal anti-inflammatory agent is selected from the group consisting of rhein, diacerein, tolmetin, and tepoxalin.

10. The method of claim 1 , wherein the administration comprises releasing the formulation from a sustained delivery device.

11. The method of claim 1 , wherein the inflamed orthopedic joint is an inflamed sacro-iliac joint.

12. A method of treating a degenerative joint disease in an inflamed orthopedic joint in a human or an animal, said joint comprising: i) opposing hyaline cartilage articular surfaces; ii) peripheral to the surfaces, a central joint space comprising a collagenous capsule; and iii) synovial fluid contained within the joint space, the method comprising directly administering into the joint space by trans-capsular administration a formulation comprising an effective amount of a compound of one of the following structural formulas:

or a salt thereof.